REGIONAL DIFFERENCE IN INDUCTION OF HEME OXYGENASE-1 PROTEIN FOLLOWING RAT TRANSIENT FOREBRAIN ISCHEMIA

Heme oxygenase (HO) is a rate-limiting enzyme in heme catabolism, the end products of which include iron, carbon monoxide and bilirubin. We investigated the changes in expression of an inducible form, heme oxyg enase-1 (HO-1), and a constitutive form, HO-2, in rat brain following 20 min of forebrain ischemia, using specific antisera for HO-1 and HO- 2. HO-1 protein was remarkably induced in brain following ischemia, wh ile the level of HO-2 protein was not noticeably affected. The level o f HO-1 protein expression was maximal at 12 h, which is in good agreem ent with the time course of the HO-1 mRNA induction. In the cortical m antle, most of the cells expressing increased HO-1 protein were identi fied as pyramidal neurons and astrocytes by their shapes and locations . In hippocampal CA-2 and CA-3 subfields, prominent induction was obse rved in astrocytes rather than in neuronal cells. By contrast, the HO- 1 protein was not detected in the CA1 subfield following the insult, a lthough the increased level of transcripts was evident in neurons and glial cells. These results suggest that not only in neuronal cells but also in astrocytes,within the CA1 subfield, there may be an impairmen t of protein metabolism, preceding the delayed CA1 pyramidal cell loss es.